Human malaria is caused by infection with protozoan parasites of the genus Plasmodium. Four species are known to cause human disease: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale and Plasmodium vivax. However, Plasmodium falciparum is responsible for the majority of severe disease and death. Recent estimates of the annual number of clinical malaria cases worldwide range from 214 to 397 million (The world health report 2002: reducing risks, promoting healthy life. Geneva: World Health Organization; Breman et al., 2004), although a higher estimate of 515 million (range 300 to 660 million) clinical cases of Plasmodium falciparum in 2002 has been proposed (Snow et al., 2004). Annual mortality (nearly all from Plasmodium falciparum malaria) is thought to be around 1.1 million (Breman et al., 2004).
Malaria also significantly increases the risk of childhood death from other causes (Snow et al., 2004). Almost half of the world's population lives in areas where they are exposed to risk of malaria (Hay et al., 2004), and the increasing numbers of visitors to endemic areas are also at risk. Despite continued efforts to control malaria, it remains a major health problem in many regions of the world, and new ways to prevent and/or treat the disease are urgently needed.
Early optimism for vaccines based on malarial proteins (so called subunit vaccines) has been tempered over the last two decades as the problems caused by allelic polymorphism and antigenic variation, original antigenic sin, and the difficulty of generating high levels of durable immunity emerged, and with the notable failures of many promising subunit vaccines (such as SPf66) have led to calls for a change in approach towards a malaria vaccine. Consequently, this growing sense of frustration has lead to the pursuit of different approaches that focus on attenuated strains of malaria parasite or irradiated Plasmodium falciparum sporozoites (Hoffmann et al., 2002). Similarly, both the limited success achieved to date with protein-based vaccines and the recognition that cell mediated immunity may be critical to protection against hepatic and perhaps blood stages of the parasite has led to a push for DNA and vectored vaccines, which generate relatively strong cell mediated immunity. Unfortunately, DNA vaccines have demonstrated poor efficacy in humans with respect to antibody induction (Wang et al., 2001). Thus, there remains a need for methods of treating and preventing malaria.